Fluorinated alcohol and ether derivatives thereof



United States Patent 3,352,928 FLUQRINATED ALCOHGL AND ETHER DERIVATIVESTHEREOF Everett E. Gilbert and Benjamin Veldhuis, Morristown, N.J.,assignors to Allied Chemical Corporation, New York, N.Y., a corporationof New York No Drawing. Filed Sept. 14, 1965, Ser. No. 487,334

1 Claim. (Cl. 260-633) This invention relates to1,1,3,3-tetrafluoro-2-propanol, a novel alcohol, and to itscorresponding methyl and ethyl ether derivatives.

Fluorinated alcohols of various types, including 2,2,3,3-tetrafiuoro-l-propanol, are known. 1,1,3,3-tetrafiuoro-2- propanol,however, is a heretofore unknown alcohol having unusual and unexpectedproperties. This alcohol exhibits exceptionally high solubility forpolyamides, such as nylon, and may be employed as solvent inpolyamidebased adhesives. In such use, the alcohol has been found to becompletely stable, even when the adhesives are subjected to elevatedtemperatures.

The novel methyl and ethyl ether derivatives of this invention possessoutstanding utility as general inhalation anesthetics when administeredto anesthetic-susceptible organisms.

1, l,3,3-tetrafluoro-2-propanol, HF CCHOHCF H, is readily prepared byreacting 1,1,3,3-tetrafiuoroacetone with sodium borohydride attemperature of about to 50 C. in the presence of a solvent for thereactants, such as diethylene glycol dimethyl ether. After the reactionis complete, the reaction mixture is added to an aqueous sulfuric acidsolution and distilled to give a mixture of water and the desiredalcohol. The distillate is dehydrated and then subjected to vacuumdistillation to yield the alcohol in pure form (boiling point about 109C.).

The methyl and ethyl ether derivatives of this invention, HF C-CHOCH CFH (1,1,3,3-tetrafluoroisopropyl methyl ether) and HF CCHOC H CF H(1,1,3,3- tetrafiuoroisopropyl ethyl ether), respectively, are readilyprepared by reacting an aqueous solution of1,1,3,3-tetrafluoro-Z-propanol with sodium hydroxide and then withdimethyl or diethyl sulfate at temperature of about 0 to 50 C. Theresulting oil layer is separated, dried and then distilled to give thedesired ether derivative.

The following examples will serve to illustrate preparation of the novelalcohol and ether derivatives of this invention. In the examples, partsare by weight.

Example J.-Pr0duction of 1,1,3,3-tetrafluoro-Z-propanol 47 parts ofsodium borohydride in 473 parts of diethylene glycol dimethyl ether wereplaced in a reaction vessel equipped with a mechanical stirrer. 520parts of 1,l,3,3- tetrafluoroacetone were then added over a period of 2%hours at C. The resulting reaction mixture was allowed to standovernight and was then added to a mixture of 250 parts of water and 138parts of concentrated sulfuric acid. Solid boric acid by-product wasfiltered off, and the solution was distilled to give a mixture of waterand l,1,3,B-tetrafluoro-Z-propanol boiling at about 104 C. Treatment ofthe distillate with anhydrous sodium sulfate gave 875 parts of a mixtureof water and the alcohol having enhanced alcohol content. A 100 partaliquot of this mixture was dehydrated and purified by vacuumdistillation (at 5 mm. Hg and 90 C.) from 200 parts of 100% sulfuricacid to yield 21 parts of crude anhydrous alcohol. Redistillation of thecrude alcohol gave pure 1,1,3,3-tetrafluoro-2-propanol boiling at about109 C.

Infrared spectrographic analysis of the alcohol showed OH absorption at2.85 microns and CF absorption at 8.6 to 9.7 microns. The structure ofthe alcohol was confirmed by nuclear magnetic resonance analysis.

Elemental analysis of the alcohol gave the following results:

Calculated: F, 57.6%; H, 3.0%. Found: F, 59.0%; H, 3.2%.

Example 2.-Production of 1,1,3,3-tetraflu0r0- isopropyl methyl ether Amixture of 180 parts of water and 40 parts of 50% sodium hydroxidesolution was placed in a reaction vessel provided with a mechanicalstirrer. An aqueous solution of parts of the crude alcohol prepared inExample 1 was then added over a period of 20 minutes at 20 C. 63 partsof dimethyl sulfate were next added over a 30 minute period at about 10C. The resulting reaction mixture was warmed to 50 C. and held at thistemperature for 50 minutes. An oil layer separated upon cooling. Thislayer was removed, dried over magnesium sulfate and then distilled togive 35 parts of 1,1,3,3-tetrafluoroisopropyl methyl ether having aboiling point of 81-815 C.

Infrared spectrographic analysis of the methyl ether derivative showedCF absorption at 8.6 to 9.7 microns and ether linkage (CH OC) absorptionat 9.8 to 10.1 microns. The structure of the methyl ether derivative wasconfirmed by nuclear magnetic resonance analysis.

Elemental analysis of the methyl ether derivative was as follows:

Calculated: F, 52.0%; H, 4.1%. Found: F, 50.7%; H, 4.1%.

Example 3.-Pr0ductz'0n of 1,I,3,33-tetrafluoro isopropyl ethyl etherWhen the process of Example 2 is carried out using diethly sulfate inplace of dimethyl sulfate, 1,1,3,3-tetrafluoroisopropyl ethyl ether isobtained as product.

The alcohol of this invention gave a clear 15% solution of nylon 6 uponwarming the components together on a steam bath at about C. for severalhours. The resulting solution was suitable for use as a nylon adhesive.When the known isomeric primary alcohol, 2,2,3,3-tetrafluoro-l-propanol,is used for the same purpose, it tends to become unstable, particularlyat slightly elevated temperatures, releasing hydrogen fluoride duringuse. This presents a serious shortcoming of the primary alcohol.Furthermore, the primary alcohol fails completely to dissolve the highquantity of nylon which the alcohol of this invention dissolves withease.

A standard test for evaluating the methyl ether derivative of thisinvention as an inhalation anesthetic was carried out. Details of thetest, which is similar to that described by Robbins, J. Pharmacol,Exper. Therap., 86, 197-204 (1946), are as follows:

Ten mice (five in each of two 6.3 liter animal jars) were used for eachdose level. A minimum of three graded doses, injected at 0.1 ml. per 10seconds, was used to establish that dose which caused 50% of the mice tolose the righting reflex in five minutes. The concentration ofanesthetic vapor in the jar was calculated using the ideal gas law (seeCarson et al., Anesthesiology, 23, 187 (1962)). The AD (volume percentof compound required to anesthetize 50% of the mice used) was determinedby plotting the data on log-probit graph paper (see Miller et al., Proc.Soc. Exp. Biol. and Med., 57, 261 (1944)). Essentially the sameexperimental procedure was used to determine the LD (dosage required tokill 50% of the mice).

The AD is obtained upon testing the methyl ether derivative was 1.40,and the LD obtained was 103. The AI (anesthetic index=LD +AD was,therefore, 7.3. The AI is a measure of the margin of toxic safety of thecompound; the higher the number, the less toxic the compound relative tothe dosage needed to induce anesthesia. The three most highly developedcommercial fiuorinated anesthetics (Fluomar (trifluoroisopropyl vinylether); Roflurane (Z-bromo-Z-fluoro-l, l-difluoroethyl ether); Penthrane(2,2-dichl0ro-1,1-difiuoroethyl ether)) have AI values in the range of3.3 to 4.5. It is apparent, therefore, that the methyl ether derivativepossesses unusually low toxicity.

Since various changes and modifications may be made in the inventionWithout departing from the spirit thereof, the invention is deemed to belimited only by the scope of the appended claim.

We claim: 1,1,3,3-tetrafiuoro-2-pr0panol.

References Cited UNITED STATES PATENTS 4/1964 Castle 260-633 OTHERREFERENCES Neunhoefier et al., Chem. Abstracts, vol. 55 (1961).

10 LEON ZITVER, Primary Examiner.

J. E. EVANS, Assistant Examiner.

